Date of Graduation

Spring 3-31-2019

Document Type

Thesis

Degree Name

Master of Science in Chemistry

College/School

College of Arts and Sciences

Department/Program

Chemistry

First Advisor

Dr. Janet Yang

Second Advisor

Dr. Ryan West

Third Advisor

Dr. Nicole Thometz

Abstract

ATP-Binding Cassette (ABC) Transporters are a superfamily of integral membrane proteins that have been found embedded in both the cellular membranes and internal organelles of all species yet analyzed (1). This extreme conservation throughout the tree of life is due to their vitally critical and broad task of transporting all manner of things into and out of the cell and related organelles. This broadness of responsibility has led to an abundant diversity of this family, which in turn, has allowed life to adapt to the many environments found on Earth. While the importance and variability of this family is abundantly clear, many mechanistic and regulatory questions remain. The diversity which has made this family so useful in the natural world has resulted in a huge challenge in the scientific world: elucidating the many mechanisms this family has developed to perform its many functions.

The scientific community has so far been able to identify overarching features of all ABC transporters such as the Walker A and Walker B motifs (1); however, the mechanisms of individual transporters remain undiscovered. In my research, I focus on a specific ABC transporter called NaAtm1 (Novosphingobium aromaticivorans ABC transporter of mitochondria 1), which has been shown to mediate transition metal export in its host species (2). While some transition metals (e.g. iron and copper) are essential for certain cellular processes such as respiration and enzyme catalysis, other metals (e.g. cadmium and mercury) can be very toxic. Due to this extreme dichotomy, a cell’s ability to distinguish between friend and foe is of the utmost importance, and therefore is a highly regulated process.

My goal during this program was to purify NaAtm1 and create a realistic in-vitro environment to analyze and better understand the full mechanism of this transporter, to determine why it exports some metals while leaving others alone, and to understand the regulatory processes that control it.

References

[1] Davidson, A. L.; Dassa, E.; Orelle, C.; Chen, J. Structure, function, and evolution of bacterial ATP-binding cassette systems. Microbiology and Molecular Biology Reviews 2008, 72(2), 317–364.

[2] Lee, J. Y.; Yang, J. G.; Zhitnitsky, D.; Lewinson, O.; Rees, D. C. Structural basis for heavy metal detoxification by an Atm1-type ABC exporter. Science 2014, 343(6175), 1133–11

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